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Immunology xi immunodeficiency
 

Immunology xi immunodeficiency

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    Immunology xi immunodeficiency Immunology xi immunodeficiency Presentation Transcript

    • Imunodeficiency states
      • Primary
        • Caused by defined genetic defects
        • Usually rare, but severe (exception: IgA deficiency)
      • Se condary
        • Consequence of so m e other disease, treatment, environmental factors…
        • Usually frequent, but usually clinically mild (ex c eptions: HI V disease, secondary aganulocytosis).
    • Severe combined immunodeficiency (SCID)
      • Early clinical manifestation (weeks-months)
      • Severe and complicated infections affecting respiratory and gastrointestinal tract and the skin
      • Failure to thrive
      • Frequent diarrhea
      • Usually lymphocytopenia
      • T-cell def i ciency, B cell present in some patients
      • Decreased immunoglobulin levels
    • SCID, t-GVHR, generalised BCG-itis
    • SCID infections caused by atypical patogens
      • Pneumocystis pneumonia
      • Cytomegalovirus pneumonitis
      • Disseminated BCG-itis
      • Infections caused by atypical mycobacteria
      • Candidiasis of oropharynx, skin
    • Pa tient with SC ID
    • Immunoglobulin Deficiencies Clinical manifestations begins at 6-12 months (or late). Susceptibility to infection by encapsulated bacteria (Pneumococcus, Haemophilus) . Respiratory tract predominantly affected; patients suffer from recurrent otitis media,bronchitis, sinusitis, pneumonia . Some patients also suffer from meningitis or chronic diarrhea .
    • X-linked agammaglobulinemia
      • Only boys affected
      • Clinical manifestation usually begins at 6-12 months
      • Severe and complicated respiratory tract infections.
      • Very low levels of all immunoglobulin isotypes.
      • B-cell not detected
    • Common variable immunodeficiency (CVID)
      • Both sexes affected
      • Clinical manifestation initiates at any age
      • Frequent and severe respiratory tract infections
      • P r oneness to autoimmune diseases
      • Vari ab le decrea s e of immunoglobulin isotypes, usually markedly decreased I gA and I gG leves
      • B-lymphocy t es usually present
    • Selective IgA deficiency
      • Frequency: 1:400
      • Usually only mild manifestation
      • Predominantly respiratory tract infections
      • Patients are prone to autoimmune diseases
      • Beware of anti-IgA antibodies that can cause a severe anaphylactic reaction after artificial IgA administration (by blood, immunoglobulin derivates)!
      • T-cell Deficiences
      • Early onset of clinical manifestation .
      • Extreme susceptibility to viral, fungal, mycobacterial, and protozoal infections .
      • - Respiratory system most frequently affected, but also other systems can be involved .
    • DiGeorge syndrome
      • Defect in embryonic development of the 3rd and 4th pharyngeal pouches.
      • Cardiovascular defects
      • Hypoparathyroidism  hypocalcemia  seizures
      • Thymic hypoplasia  T cell def i ciency
      • Typical facies: hypertelorism, micrognatia, low-set, posterior rotated ears.
    • DiGeorge syndrom e
    • DiGeorge syndrom e
    • Complement deficiencies
      • Deficiency of C1-C4: autoimmune systemic disorders, susceptibility to bacterial infections
      • Deficiency C5-C9: susceptibility to bacterial infections, mainly to meningococcal meningitis
      • Defici e ncy of C1 INH: hereditary angioedema
    • Hereditary angioedema
      • Deficiency of C1 inhibitor (C1 INH)
      • Uncontrolled activation of the complement system after trauma, infection, surgical operation....
      • Vasoactive peptides ( bradykinin, C3a,C5a) cause increased vascular permeability
      • Oedema of the skin, respiratory tract (dyspnoe), gastrointestinal tract (cramps, vomiting)
    • HEREDITARY ANGIOEDEMA (HAE)
    • Phagocytic dysfunction
      • Early onset of clinical manifestation
      • Susceptibility to bacterial and fungal infections
      • A b scess formation, mainly of the skin, periproctal area, liver, but any area may be affected.
    • Chronic granulomatous disease
      • Recurrent abscesses mainly of the liver, lungs, periproctal area, suppurative lymphadenitis, osteomyelitis
      • Infections are caused mainly by catalase-positive organisms: St. aureus, Candida sp. , Serratia marcescens
      • Usually early onset of symptoms
      • Production of reactive metabolites of oxygen is disturbed (defect of NADPH oxidase)
    • Wiskott-Aldrich syndrome
      • X-linked disease
      • Thrombocytopemia  bleeding tendency
      • Severe eczema
      • Immunodef i ciency
      • Severe allergic and autoimmune manifestations
      • B-cell lymphomas
    • Wiskott-Aldrich syndrom e
    • Ataxia telangiectasia
      • Autosomal recessive
      • Progressive ce r ebe llar ataxia
      • Tela n giectasis especially on ear lobes and conjunctival sclera
      • Immunodeficiency
      • Frequent tumors
      • Cause: m utation in ATM gene
    • A taxia telangiectasia
    • Treatment of primary immunodefciencies
      • SCID and other severe immunodeficiencies: bone marrow transplantation, gene therapy in some cases.
      • Antibody deficiencies: immunoglobulin replacement
      • Antibiotic prohylaxis
    • Clinical use of non-specific immunoglobulin derivates
      • Types of derivates:
        • „ Normal immunoglobulin“ - for intramuscular use . Used very rarely at present bcause only low dose can be given..
        • Intravenous immunoglobulins , subcutaneous immunoglobulins - can be used in high doses
      • Indications:
        • Replacement treatment in patients with antibody deficiencies
        • Prophylaxis of infections against which there is no specific immunoglobulin derivate (hepatitis A)
        • High doses of i.v. immunoglobulins are used in autoimmune diseases , systemic vasculitic diseases.
    • Causes of secondary immunodeficiency
      • Metabolic - ur e mia, diabetes, malnutr it ion
      • Iatrogenic – cytostatics, immunosuppressants
      • Malignat tumors
      • Viral infections - HIV , CMV , measles, infectious mononucleosis
      • Splenectomy
      • Stres s
      • Injuries, operations, general anestes ia
    • Imunodeficiency after splenectomy
      • Disturbed phagocytosis, decreased production of antibodies.
      • The most severe complication is hyperacute pneumococal sepsis.
      • Prevention: vaccination against Pneumococcus, Haemophilus infl. B, Meningococcus. PNC pro p hylaxis.
    • Secondary hypogammaglobulinemia
      • Decreased production of immunoglobulins
        • Chronic lymphatic leukemia
        • Lymphoma
        • Myeloma
      • Loss of immunoglobulins
        • Nephrotic syndrome
        • Exudative enteropathy
    •  
    • Ways of transmission
      • Sexual
      • Parenteral – intravenous drug addicts
      • previously blood products
      • 3. Vertical – mother to child – transplacental, during delivery, by brestfeeding
    •  
    • Infe ction of CD4+ cell by HIV
    • HIV Cy cle
    •  
    • Classification of HIV disease (CDC)
      • 3 clinical categories
      • A Asymptomatic disese
      • B „small“ opportunistic infections
      • C „big“ opportunistic infections and other states that define AIDS
    • Clinical category A
      • Accute (primary) HIV infection
      • Asymptomatic HIV infection
      • Persistent generalised lymphadenopathy (PGL)
    • HIV PRIMOINFECTION
      • Acute retroviral syndrome, („mononucleosis-like syndrome“)
      • Present in 50-70% patients
      • 2-6 weeks after infection
    • Clinical presentaioon of HIV primoinfection
      • Fever, lympadenopathy, pharyngitis
      • Rash
      • Myalgia, arthralgia, diarrhoea, cephalea
      • nausea, vomiting
      • thrush
      • Neurologic symptoms
      • A phtous stomatitis
    • Perzistent generalized lympadenopathy -
      • More than 3 months
      • 1/3 HIV-infected persons
      • Lymph nodes 0,5-2,0 cm, painless
    • Clinical category B
      • Fever >38,5 C more than 1 month
      • Diarrhoea more than 1 month
      • Oropharyngea candidiasis
      • Vulvovaginal candidiasis
      • (chronic or difficult to treat)
      • Recurrent herpes zoster
    • Clinical category C (AIDS)
      • Pneumocystis pneumonia
      • Brain abscess caused by toxoplasma
      • Esofageal, tracheal, bronchial or lung candidiasis
      • Chronic anal herpes, herpetic bronchitis, pneumonia
      • CMV retinitis, generalized CMV infection
      • Progressive multifocal leukoecephalopathy
      • Mycobacterial infections
    • Opportunistic Infections in AIDS Patients - Pneumonia due to Pneumocystis jiroveci ( carinii ) - Toxoplasma brain abscess - Cytomegalovirus infection (retinitis, colitis) - Mycobacterial infections - Herpes virus and Varicella-Zoster infections
    • Clinical category C ( AIDS ) - tumors
      • Kaposhi sarcoma
      • Brain lymphoma
    • Kaposh i sar coma
    • Kaposiho sarkom
    • Wasting syndrome
    • Treatment of HIV-disease
      • Antiretroviral
        • Nucleoside inhibitors of reverse transcriptase : azidothymidin (syn. zidovudin), didanosin, zalcitabin, stavudin, lamivudin
        • Nonnucleoside inhibitors of reverse transcriptase : Nevirapin, delavirdin, efavirenz
        • HIV protease inhibitors : Saquinavir, ritonavir, indinavir
      • Prophylaxis of Pneumocystis carinii pneumonia (co-trimoxazol), antiviral and antimycotic antibiotics
    • Strategy of treatment
      • HAART - Highly
      • Active
      • Anti
      • Retroviral
      • Therapy
      • Mega-HAART
    • Diagnos is of HIV infe ction
      • Detection of anti-viral antibodies
        • ELISA
        • Western blott
      • Detection of antigen p 24